phytoestrogens and Prostatic-Hyperplasia

Phytoestrogens are non-steroidal estrogens widely distributed in many kinds of plants. They are natural compounds structurally similar to estrogen and with estrogenic or anti-androgenic activities. Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are androgen-dependent and associated with age. Recently, in many epidemiological and experimental researches, it has been reported that phytoestrogens play a role in the prevention and treatment of PCa and BPH. Regulation of sexual hormones, inhibition of cell proliferation, induction of cell apoptosis and anti-oxidation of such plant estrogens may be involved in the mechanisms.

Topics: Animals; Disease Models, Animal; Humans; Male; Phytoestrogens; Prostatic Hyperplasia; Prostatic Neoplasms; Rats; Rats, Sprague-Dawley; Rats, Wistar

Topics: Diet; Humans; Male; Phytoestrogens; Prostatic Hyperplasia

The prostate has only one function, namely to secrete fluid containing substances that are needed for reproduction. This requires an extremely high concentration of androgens in the tissues. Benign prostatic hypertrophy (BPH) seems to be related to the long-term exposure of the prostate to the strong androgen 5alpha-dihydrotestosterone (DHT) and, possibly, to estrogens. The relation between prostate cancer and androgens is suggested to be U-shaped, with both extremes of androgen concentrations being associated with increased risk of invasive cancer. In the treatment of patients with BPH, the lipidic liposterolic extracts of Serenoa repens were as effective as the pharmaceutical inhibitors of the 5alpha-reductase enzyme or alpha1-adrenergic blockers in relieving urinary symptoms. In addition to moderately inhibiting the 5alpha-reductase activity, Serenoa seems to exert anti-inflammatory and complementary cellular actions with beneficial effects on the prostate. Unlike the pharmaceutical 5alpha-reductase inhibitors, finasteride and dutasteride, Serenoa does not suppress serum PSA, facilitating the follow-up and the early detection of prostate cancer. We suggest a strategy to prevent prostate cancer that aims at providing men with partial androgen deficiency correct testosterone substitution with a sustained release buccal bio-adhesive tablet. In addition, food supplementation with extracts of Serenoa repens and a combination of the antioxidants selenium, (cis)-lycopene and natural vitamin E, together with fish oil rich in long-chain polyunsaturated essential fatty acids of the omega-3 group seems warranted. Clearly, a holistic approach including careful clinical and biological monitoring of the aging man and his prostate remains mandatory.

Topics: Aged; Androgen Antagonists; Androgens; Antioxidants; Hormone Replacement Therapy; Humans; Male; Phytoestrogens; Phytotherapy; Plant Preparations; Prostatic Hyperplasia; Prostatic Neoplasms; Serenoa

Both benign hyperplasia (BPH) and cancer of the prostate are manifest in men beyond the age of 50. Approximately 50% of men greater than 50 years of age will suffer from the symptoms associated with BPH, especially from bladder outlet obstruction. With the ever-increasing proportion of the population over 65 years of age worldwide, BPH is becoming an important medical problem as the world moves into the next millennium. Cancer of the prostate is the second most commonly diagnosed cancer after skin cancer in the male population of the United States, and the second most common cause of death from cancer after that of the lung. Overall, around the world the incidence of carcinoma of the prostate is increasing annually by 2-3%. Both race and geographical location have a profound influence of the prevalence of prostate cancer worldwide. Black men in the USA have the highest incidence, while the incidence is much lower in Asian men from China, Japan and Thailand. Although the prostate gland is androgen-dependent, it is now recognized that the biological actions of endocrine-related factors, such as androgens, oestrogens, glucocorticoids and certain dietary and environmental factors, are mediated within the gland by various growth regulatory factors. The growth regulatory factors such as epidermal growth factor (EGF), keratinocyte growth factors (KGF), fibroblast growth factors (FGFs) and insulin-like growth factors II and I are mitogenic and directly stimulate cell proliferation under the modulating influence of steroid hormones. Steroids are therefore essential but not directly responsible for cell proliferation. Certain plant compounds such as isoflavonoids, flavonoids and lignans have been proposed as cancer protective compounds in populations with low incidences of prostate diseases. In particular, soya contains the isoflavone genistein, a compound with many properties which could influence both endocrine and growth factor signalling pathways.

Topics: Estrogens, Non-Steroidal; Humans; Isoflavones; Lignans; Male; Phytoestrogens; Plant Preparations; Prostatic Diseases; Prostatic Hyperplasia; Prostatic Neoplasms

Reliable and adequate animal models are required, not only for investigation of etiology, pathogenesis, and treatment of prostate cancer, but also for chemoprevention of prostatic carcinogenesis.. Animal models for the study of premalignant changes in the prostate are reviewed in the paper, with specific reference to the neonatally estrogenized mouse model.. Neonatal treatment of newborn Han:NMRI mice with synthetic non-steroidal estrogen, diethylstilbestrol (DES; 2 micrograms/pup on days 1-3 after birth) promoted hyperplastic and dysplastic changes in the periurethral region of the prostate at the age of 9-18 months. Dietary soy partially inhibited the development of prostatic dysplasia in these neonatally estrogenized animals, which may be due to phytoestrogens contained in soy-rich food.. Prostatic cancer and its possible precursors develop spontaneously, or can be induced by different chemical and hormonal manipulations in certain animal species and strains. Neonatal estrogenization of the mouse results in prostatic dysplasia, which can be partially prevented by dietary soy. There are morphological similarities between human prostatic intraepithelial neoplasia (PIN) and dysplastic changes in rodent prostates, but more data is needed before these dysplastic lesions can be considered equivalent to human PIN.

Topics: Animals; Animals, Newborn; Diet; Diethylstilbestrol; Disease Models, Animal; Estrogens, Non-Steroidal; Glycine max; Isoflavones; Male; Mice; Phytoestrogens; Plant Preparations; Prostate; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Rats; Rats, Inbred F344

Knockout of ERβ in the mouse leads to nuclear expression of epidermal growth factor receptor (EGFR) in the prostate. To examine whether ERβ plays a similar role in the human prostate, we used four cohorts of men: 1) a Swedish cohort of normal prostates and PCa (prostate cancer) of different Gleason grades; 2) men with benign prostatic hyperplasia (BPH) treated with the 5α-reductase inhibitor, finasteride, and finasteride together with the ERβ agonists, soy isoflavones; 3) men with PCa above Gleason grade 4 (GG4), treated with ADT (androgen deprivation therapy) and abiraterone (AA), the blocker of androgen synthesis for different durations; and 4) men with GG4 PCa on ADT or ADT with the AR (androgen receptor) blocker, enzalutamide, for 4 mo to 6 mo. In men with BPH, finasteride treatment induced EGFR nuclear expression, but, when finasteride was combined with isoflavones, EGFR remained on the cell membrane. In GG4 patients, blocking of AR for 4 mo to 6 mo resulted in loss of ERβ and PTEN expression and increase in patients with nuclear EGFR from 10 to 40%. In the men with GG4 PCa, blocking of adrenal synthesis of testosterone for 2 mo to 7 mo had the beneficial effect of increasing ERβ expression, but, on treatment longer than 8 mo, ERβ was lost and EGFR moved to the nucleus. Since nuclear EGFR is a predictor of poor outcome in PCa, addition of ERβ agonists together with abiraterone should be considered as a treatment that might sustain expression of ERβ and offer some benefit to patients.

Topics: Active Transport, Cell Nucleus; Androgen Antagonists; Androstenes; Animals; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Biopsy; Cell Nucleus; Cohort Studies; ErbB Receptors; Estrogen Receptor beta; Finasteride; Humans; Male; Mice; Mice, Knockout; Neoplasm Grading; Nitriles; Phenylthiohydantoin; Phytoestrogens; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; PTEN Phosphohydrolase; Receptors, Androgen; Receptors, Estrogen

Pueraria mirifica (PM) is a medicinal plant native to Thailand contained high amount of phytoestrogen and possesses anticancer activity. This study reports the effect of P. mirifica extract, phytoestrogen of diadzein and genistein for its benign prostate hyperplasia properties in testosterone-induced prostate hyperplasia in male Sprague Dawley rats. The P. mirifica extract was evaluated for its total phenols, flavonoid and antioxidant activity using DPPH, FRAP and metal chelating assay. The assessment of P. mirifica, diadzein and genistein against benign prostate hyperplasia was determined in testosterone-induced prostate hyperplasia in male Sprague Dawley rats. The total phenol was higher than flavonoid but showed low antioxidant activity of DPPH, FRAP and metal chelating. The aqueous PM extract at 1000 mg/kg significantly increased testosterone levels in testosterone-induced rats by 13% while diadzein and genistein increased it by 11% and 17% respectively. However, levels of FSH, LH, triglyceride and HDL are not affected by the oral administration of PM, diadzein and genistein to the rats. Similarly, total protein, albumin, globulin, total bilirubin, conjugated bilirubin, alkaline phosphatase, alanine aminotransferase, AST, and G-glutamyltransferase showed no significant difference as compared with negative control rats. The body weight of the rats, testis, kidney and liver showed no toxic effect. The zinc content increased significantly and the zinc transporter gen of ZnT4 and ZIP4 highly expressed suggesting that the PM, diadzein and genistein plays essential role in modulating prostate zinc homeostasis. Similarly, the expression of IL-6, AR and ER was significantly reduced indicating functioning in regulation of prostate growth and acts as anti-inflammatory role in preventing BPH. In conclusion, the results indicated that PM reduced BPH and contributed to the regulation in the zinc transport expression of the prostate cells in the benign prostate hyperplasia (BPH).

Topics: Animals; Antioxidants; Genistein; Hyperplasia; Isoflavones; Male; Membrane Transport Proteins; Phytoestrogens; Plant Extracts; Prostate; Prostatic Hyperplasia; Pueraria; Rats; Rats, Sprague-Dawley; Testis; Testosterone; Thailand; Zinc

Bisphenol A (BPA) is one hormonally active chemical with potential deleterious effects on reproductive organs, including breast and prostate. In contrast, genistein (GEN) is the major phytoestrogen of soy that presents potential protective effects against hormone-dependent cancers, including that of the prostate. Thus, pregnant Sprague-Dawley rats were treated with BPA at 25 or 250 μg/kg/day by gavage from gestational day (GD) 10-21 with or without dietary GEN at 250 mg/kg/chow (∼5.5 mg/kg/day). Then, male offspring from different litters were euthanized on post-natal day (PND) 21 and 180. At PND21, BPA 25 exposure induced early prostatic changes while dietary GEN attenuated some deleterious actions this xenoestrogen on epithelial cell proliferation levels, androgen receptor expression and prostatic architecture in male offspring. At PND180, a significant increase in incidence of prostatic multifocal inflammation/reactive hyperplasia and atypical hyperplasia were observed in male offspring from dams that received BPA 25. On the other hand, maternal GEN feeding attenuated some the adverse effects of BPA 25 on prostate disease at late-in-life. This way, the present findings point to preventive action of dietary GEN on deleterious effects of gestational BPA exposure in both early and late prostate development in offspring F1.

Topics: Animals; Benzhydryl Compounds; Cell Proliferation; Dietary Supplements; Dose-Response Relationship, Drug; Estrogens, Non-Steroidal; Female; Genistein; Male; Maternal Nutritional Physiological Phenomena; Phenols; Phytoestrogens; Pregnancy; Prenatal Exposure Delayed Effects; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Rats, Sprague-Dawley; Receptors, Androgen; Specific Pathogen-Free Organisms; Weaning

Androgen and estrogen play an important role in the pathogenesis of benign prostatic hyperplasia (BPH). Estrogen exerts its action through two distinct estrogen receptors (ERs) either ER-α or ER-β. The phytoestrogenic property of silymarin (SIL) has been previously characterized. Thus, this study examined the protective effect of SIL against testosterone-induced BPH in rats. In an initial dose-response study, SIL in a dose of 50mg/kg was the most effective in preventing the rise in prostate weight, prostate weight/body weight ratio and histopathologic changes induced by testosterone. Testosterone significantly decreased ER-β and increased ER-α and AR expressions as compared to the control group and these effects were significantly ameliorated by SIL. Furthermore, SIL significantly protected against testosterone-provoked decline in mRNA expression of P21(WAF1/Cip1) and Bax/Bcl-xl ratio as well as caspase-3 activity. SIL minimized the number of proliferating cell nuclear antigen (PCNA) positive cells as compared to testosterone-treated group. Moreover, SIL significantly blunted the inducible NF-κB expression and restored the oxidative status to within normal values in the prostatic tissues. Collectively these findings elucidate the effectiveness of SIL in preventing testosterone-induced BPH in rats. This could be attributed, at least partly, to its phytoestrogenic, pro-apoptotic and anti-oxidative properties.

Topics: Animals; Antioxidants; Apoptosis; Body Weight; Caspase 3; Cell Proliferation; Dose-Response Relationship, Drug; Immunohistochemistry; Male; NF-kappa B; Organ Size; Oxidative Stress; Phytoestrogens; Proliferating Cell Nuclear Antigen; Prostate; Prostatic Hyperplasia; Rats; Rats, Sprague-Dawley; Receptors, Androgen; Receptors, Estrogen; RNA, Messenger; Silymarin; Testosterone

To assess the effectiveness of the traditional Chinese herb Phellodendron amurense in treating urological disorders.. Prostate smooth muscle relaxant activity of an extract from the bark of Phellodendron amurense was tested on contractions of isolated rat prostate gland induced by electrical nerve stimulation and direct muscle stimulation.. Electrical field stimulation (0.5 ms, 60V, 1-20 Hz) induced nerve mediated contractions of isolated rat prostate were inhibited by Phellodendron amurense extract dissolved in either dimethylsulfoxide (DMSO), acetic acid or water (P

Topics: Adrenergic Agonists; Animals; Cholinergic Agonists; Drugs, Chinese Herbal; Electric Stimulation; In Vitro Techniques; Isometric Contraction; Male; Muscle, Smooth; Phellodendron; Phytoestrogens; Plant Bark; Prescription Drugs; Prostate; Prostatic Hyperplasia; Purinergic Agonists; Rats; Rats, Sprague-Dawley

To investigate the preventive effect of the phytoestrogen daidzein on prostatic hyperplasia induced by testosterone in rats.. Thirty-six male adult Sprague-Dawley rats were equally randomized into 6 groups: Group I and II (normal control and model, treated with 1 ml distilled water by oral gavage), and Group III-VI (low-, medium- and high-dose daidzein and positive control, respectively given daidzein at 2, 20 and 100 mg/kg and diethylstilbestrol at 0.1 mg/kg once a day for 90 days). From the 91st day , Group III-VI were treated with subcutaneous injection of testosterone at 7.5 mg/kg/d for 10 days to induce prostatic hyperplasia. The wet weight and the index of the prostate were obtained, its morphological changes detected and the changes of ERalphaa and ERbeta expressions in the prostate observed by immunohistochemistry.. Compared with the model group, the wet weight and the index of the prostate were significantly reduced in the 3 daidzein groups and the positive control group (P < 0.05 or P < 0.01). Medium- and high-dose daidzein induced a more obvious alleviation of prostate hyperplasia, characterized by thinner epithelia, decreased secretions in the glandular cavity and reduced interstitial tissues. The expression of ERalpha showed no significant difference between the model group and the other groups, while that of ERbeta was markedly decreased in the daidzein-treated groups as compared with the normal control or the model group.. The phytoestrogen daidzein has some preventive effect on prostatic hyperplasia induced by testosterone in rats.

Topics: Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Isoflavones; Male; Phytoestrogens; Prostate; Prostatic Hyperplasia; Random Allocation; Rats; Rats, Sprague-Dawley; Testosterone

To compare phytoestrogen tissue levels in men with small-volume benign prostatic hyperplasia (BPH), large-volume BPH, and prostate cancer (PCa).. Prostatic tissue samples of men consuming a Western diet who underwent surgery for BPH (n = 63) or PCa (n = 31) were collected and frozen at -40 degrees C. In the tissue samples, the enterolactone and genistein levels were determined in duplicate by monoclonal antibody-based immunoassays. We subsequently compared the tissue levels in patients with BPH and PCa and studied the impact of enterolactone and genistein on prostate volume.. The enterolactone tissue levels were comparable in patients with BPH and PCa and revealed no correlation to prostate volume. The genistein tissue levels tended to be lower in patients with PCa (median 8.4 ng/g dry weight) compared with the entire BPH group (11.0 ng/g dry weight; P = 0.072). In addition, the genistein tissue levels were significantly greater in men with small-volume BPH (median 20.9 ng/g dry weight) compared with those with large-volume BPH (8.8 ng/g dry weight; P = 0.023).. Our data suggest an involvement of genistein in the pathogenesis of BPH and, possibly, of PCa. The impact of enterolactone is currently unknown.

Topics: 4-Butyrolactone; Adenocarcinoma; Aged; Aged, 80 and over; Diet; Genistein; Humans; Lignans; Male; Middle Aged; Organ Size; Phytoestrogens; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

To explore the inhibitive effect of soybean isoflavone on benign prostatic hyperplasia in rats.. By subcutaneously injecting testosterone propionate to induce prostate hyperplasia in rats, the changes of prostate wet weight, prostatic index, morphological change, prostate-specific acid phosphatase (PAP), acid phosphatase in the control, the model, low, moderate, high dose of soybean isoflavone groups were observed.. The ventral prostate wet weight, prostatic index, and PAP in the low, moderate, and high dose groups were significantly lower than those in the models (P < 0.05). The ventral prostate wet weight, prostatic index, and PAP in the moderate, and high dose groups were significantly lower than those in the low dose group (P < 0.05).. Soybean isoflavone inhibits prostate hyperplasia and the increase of acid phosphatase and PAP in a dose-dependent manner in rats. Soybean isoflavone may serve as supplementary therapy and prevent benign prostatic hyperplasia.

Topics: Acid Phosphatase; Animals; Cell Division; Depression, Chemical; Glycine max; Isoflavones; Male; Phytoestrogens; Plant Preparations; Prostatic Hyperplasia; Prostatic Secretory Proteins; Rats; Rats, Sprague-Dawley; Testosterone Propionate

It is becoming increasingly apparent that dietary factors may play a role in the etiology of hormone dependent neoplasias. It has been hypothesized that estrogens play some role in the etiology of benign prostatic hyperplasia (BPH) in the canine. The presence of estrogen receptor binding activity in a fraction of canine urine purified by high performance liquid chromatography (HPLC) that did not correspond to estriol, estradiol, estrone or any of their primary metabolites was observed in the present study. We used thermospray-mass spectrometry and GC-MS to identify the phytoestrogens daidzein, equol, formononetin and genistein in HPLC purified fractions of urine obtained from male beagles. Using the same techniques we also confirmed the presence of daidzein and genistein in the commercial diet fed to these same dogs. Using the immature rat uterine cytosol estrogen receptor assay, relative binding affinities of 0.08, 1.1, less than 0.01 and 3.9% were obtained for daidzein, equol, formononetin and genistein, respectively when compared to estradiol (100%). In conclusion, phytoestrogens are present in urine of male beagles. Moreover, the commercial diet fed to these dogs contains isoflavones which can be converted to equol by intestinal microflora. These results suggest the need for investigations of phytoestrogens (e.g. equol) excreted into the urine daily and its relationship to the incidence and severity of BPH in the dog.

Topics: Animal Feed; Animals; Binding, Competitive; Chromans; Chromatography, High Pressure Liquid; Dogs; Equol; Estrogens; Estrogens, Non-Steroidal; Gas Chromatography-Mass Spectrometry; Genistein; Isoflavones; Male; Phytoestrogens; Plant Preparations; Prostatic Hyperplasia; Receptors, Estrogen; Reference Values